DOCSLIB.ORG

Review Article Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Review Article Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2014, Article ID 360438, 31 pages http://dx.doi.org/10.1155/2014/360438 Review Article Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal Antonio Ayala, Mario F. Muñoz, and Sandro Argüelles Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Seville, Prof Garc´ıa Gonzales s/n., 41012 Seville, Spain Correspondence should be addressed to Sandro Arguelles;¨ [email protected] Received 14 February 2014; Accepted 24 March 2014; Published 8 May 2014 AcademicEditor:KotaV.Ramana Copyright © 2014 Antonio Ayala et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown. This review paper is dedicated to Dr. Alberto Machado 1. Lipids Overview of Biological Functions and permeability. Lipids also have a key role in biology as signaling molecules. Lipids Are Classically Divided into Two Groups: Apolar and Lipids as Signaling Molecules.Themainenzymesthatgenerate Polar. Triglycerides (apolar), stored in various cells, but lipid signaling mediators are lipoxygenase, which medi- especially in adipose (fat) tissue, are usually the main form of ate hydroperoxyeicosatetraenoic acids (HPETEs), lipoxins, energy storage in mammals [1, 2]. Polar lipids are structural leukotrienes, or hepoxilins biosynthesis after oxidation of components of cell membranes, where they participate in the arachidonic acid (AA) [4, 5], cyclooxygenase that produces formation of the permeability barrier of cells and subcellular prostaglandins [4], and cytochrome P-450 (CYP) which organelles in the form of a lipid bilayer. The major lipid type generates epoxyeicosatrienoic acids, leukotoxins, thrombox- defining this bilayer in almost all membranes is glycerol- ane, or prostacyclin [4]. Lipid signaling may occur via based phospholipid [3]. The importance of the membrane activation of a variety of receptors, including G protein- lipid physical (phase) state is evidenced by the fact that lipids coupled and nuclear receptors. Members of several different may control the physiological state of a membrane organelle lipid categories have been identified as potent intracellular by modifying its biophysical aspects, such as the polarity signal transduction molecules. Examples of signaling lipids 2 Oxidative Medicine and Cellular Longevity include (i) two derived from the phosphatidylinositol phos- ∙− Haber-Weiss reaction + O O2 phates, diacylglycerol (DAG) and inositol phosphates (IPs). H 2 DAG is a physiological activator of protein kinase C [6, 7] ∙ (n+1) n + HO 2 M M and transcription factor nuclear factor-kB (NF-B), which H promotes cell survival and proliferation. Diacylglycerol also ∙ H2O2 OH + H2O interacts indirectly with other signalling molecules such as Fenton reaction small G proteins [8]. IPs are a highly charged family of Figure 1: Fenton and Haber-Weiss reaction. Reduced form of lipid-derived metabolites, involved in signal transduction transition-metals (M ) reacts trough the Fenton reaction with that results in activation of Akt, mTOR [9], and calcium- ∙ hydrogen peroxide (H2O2), leading to the generation of OH. homeostasis [10, 11]; (ii) sphingosine-1-phosphate, a sph- ∙− Superoxide radical (O2 ) can also react with oxidized form of ingolipid derived from ceramide that is a potent messen- (+1) transition metals (M ) in the Haber-Weiss reaction leading to the ger molecule involved in regulating calcium mobilization, production of M , which then again affects redox cycling. migration, adhesion, and proliferation [12–14]; (iii) the prostaglandins, which are one type of fatty-acid derived eicosanoid involved in inflammation15 [ , 16]andimmunity 3+ [17]; (iv) phosphatidylserine, a phospholipid that plays an when superoxide reacts with ferric iron (Fe ). In addition important role in a number of signaling pathways, includes totheironredoxcyclingdescribedabove,alsoanumberof other transition-metal including Cu, Ni, Co, and V can be kinases, small GTPases, and fusogenic proteins [18]; (v) the ∙ responsible for HO formation in living cells (Figure 1). steroid hormones such as estrogen, testosterone, and cortisol, ∙ which modulate a host of functions such as reproduction, The hydroperoxyl radical (HO 2) plays an important metabolism, stress response, inflammation, blood pressure, role in the chemistry of lipid peroxidation. This protonated and salt and water balance [19]. form of superoxide yields H2O2 which can react with redox active metals including iron or copper to further generate ∙ ∙ HO through Fenton or Haber-Weiss reactions. The HO 2 2. Lipids Damage by Reactive Oxygen Species is a much stronger oxidant than superoxide anion-radical and could initiate the chain oxidation of polyunsaturated One of the consequences of uncontrolled oxidative stress phospholipids, thus leading to impairment of membrane (imbalance between the prooxidant and antioxidant levels function [28–30]. in favor of prooxidants) is cells, tissues, and organs injury caused by oxidative damage. It has long been recognized that 2.1. Lipid Peroxidation Process. Lipid peroxidation can be high levels of free radicals or reactive oxygen species (ROS) described generally as a process under which oxidants such can inflict direct damage to lipids. The primary sources of as free radicals or nonradical species attack lipids containing endogenous ROS production are the mitochondria, plasma carbon-carbondoublebond(s),especiallypolyunsaturated membrane, endoplasmic reticulum, and peroxisomes [20] fatty acids (PUFAs) that involve hydrogen abstraction from through a variety of mechanisms including enzymatic reac- a carbon, with oxygen insertion resulting in lipid per- tions and/or autooxidation of several compounds, such oxyl radicals and hydroperoxides as described previously as catecholamines and hydroquinone. Different exogenous [31]. Glycolipids, phospholipids (PLs), and cholesterol (Ch) stimuli, such as the ionizing radiation, ultraviolet rays, are also well-known targets of damaging and potentially tobacco smoke, pathogen infections, environmental toxins, lethal peroxidative modification. Lipids also can be oxi- and exposure to herbicide/insecticides, are sources of in vivo dized by enzymes like lipoxygenases, cyclooxygenases, and ROS production. cytochrome P450 (see above, lipid as signaling molecules). The two most prevalent ROS that can affect profoundly ∙ In response to membrane lipid peroxidation, and accord- the lipids are mainly hydroxyl radical (HO ) and hydroper- ∙ ∙ ing to specific cellular metabolic circumstances and repair oxyl (HO 2). The hydroxyl radical (HO )isasmall,highly capacities, the cells may promote cell survival or induce mobile, water-soluble, and chemically most reactive species cell death. Under physiological or low lipid peroxidation ofactivatedoxygen.Thisshort-livedmoleculecanbepro- rates (subtoxic conditions), the cells stimulate their mainte- duced from O2 in cell metabolism and under a variety of nance and survival through constitutive antioxidants defense stress conditions. A cell produces around 50 hydroxyl radicals systems or signaling pathways activation that upregulate every second. In a full day, each cell would generate 4 antioxidants proteins resulting in an adaptive stress response. million hydroxyl radicals, which can be neutralized or attack By contrast, under medium or high lipid peroxidation rates biomolecules [21]. Hydroxyl radicals cause oxidative damage (toxic conditions) the extent of oxidative damage overwhelms to cells because they unspecifically attack biomolecules22 [ ] repair capacity, and the cells induce apoptosis or necrosis located less than a few nanometres from its site of generation programmed cell death; both processes eventually lead to and are involved in cellular disorders such as neurodegenera- molecularcelldamagewhichmayfacilitatedevelopmentof tion [23, 24], cardiovascular disease [25], and cancer [26, 27]. ∙ various pathological states and accelerated aging.
Load more

Recommended publications
  • Athero-2017.Pdf
    Author's Personal Copy Atherosclerosis 264 (2017) 100e107 Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis Deuterium-reinforced polyunsaturated fatty acids protect against atherosclerosis by lowering lipid peroxidation and hypercholesterolemia Jimmy F.P. Berbee a, b, Isabel M. Mol a, b, Ginger L. Milne c, Erik Pollock d, Geerte Hoeke a, b, Dieter Lütjohann e, Claudia Monaco f, Patrick C.N. Rensen a, b, Lex H.T. van der Ploeg g, * Mikhail S. Shchepinov g, a Dept. of Medicine, Div. of Endocrinology, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands b Leiden Metabolic Research Services, Leiden University Medical Center, Leiden, The Netherlands c Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232-6602, USA d University of Arkansas, Stable Isotope Laboratory, 850 W Dickson Street, Fayetteville, AR 72701, USA e Institute of Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, Bonn, Germany f Kennedy Institute of Rheumatology, Nuffield Dept. of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, United Kingdom g Retrotope, Inc, 4300 El Camino Real, Suite 201, Los Altos, CA 94022, USA article info abstract Article history: Background and aims: Oxidative modification of lipoproteins is a crucial step in atherosclerosis devel- Received 14 April 2017 opment. Isotopic-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to reactive oxygen Received in revised form species-initiated chain reaction of lipid peroxidation than regular hydrogenated (H-)PUFAs. We aimed at 2 June 2017 investigating the effect of D-PUFA treatment on lipid peroxidation, hypercholesterolemia and athero- Accepted 20 June 2017 sclerosis development.
    [Show full text]
  • Lipid Peroxidation As a Biochemical Marker for Oxidative Stress During Drought
    LIPID PEROXIDATION AS A BIOCHEMICAL MARKER FOR OXIDATIVE STRESS DURING DROUGHT. AN EFFECTIVE TOOL FOR PLANT BREEDING. Mateusz Labudda Department of Biochemistry, Warsaw University of Life Sciences – SGGW, Nowoursynowska 159, 02–776 Warsaw, Poland e–mail: [email protected] Key words: abiotic stress, crop breeding, lipid oxidation, malondialdehyde, reactive oxygen species, water deficit Abstract Oxidative stress can be induced by a wide range of environmental factors, including drought. One of the main cellular components susceptible to damage by reactive oxygen species are lipids (by peroxidation of unsaturated fatty acids in biological membranes). The assay of Thiobarbituric Acid Reactive Substances (TBARS) is a well–established method for monitoring lipid peroxidation. This relatively simple analytical protocol facilitates extensive screening research in plant breeding. Suggested citation: Labudda M. (2013): Lipid peroxidation as a biochemical marker for oxidative stress during drought. An effective tool for plant breeding. E-wydawnictwo, Poland, http://www.e-wydawnictwo.eu/Document/DocumentPreview/3342 1 Introduction Higher plants have developed the ability to adapt to external, and frequently harmful, environmental factors. Drought is considered to be one of the major sources of environmental stress. It seriously affects crop productivity by inhibiting plant growth and development (Anjum et al. 2011a) and results in a 50% or more reduction in average yields (Wang et al. 2003). Water stress inhibits photosynthesis, induces changes in chlorophyll content and composition, and damages the photosynthetic apparatus (Nayyar & Gupta 2006). Furthermore, dehydration of tissue inhibits photochemical activities and brings about a reduction in the activity of Calvin–Benson–Basshamn cycle enzymes (Monakhova & Chernyadev 2002). It is well established that chloroplast, mitochondria and peroxisomes are a major source of reactive oxygen species (ROS) in plant cells.
    [Show full text]
  • Chemical Synthesis, Characterization and Biological Evaluation of Methylation and Glycation Dna Adducts
    University of Rhode Island DigitalCommons@URI Open Access Dissertations 2019 CHEMICAL SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF METHYLATION AND GLYCATION DNA ADDUCTS Qi Tang University of Rhode Island, [email protected] Follow this and additional works at: https://digitalcommons.uri.edu/oa_diss Recommended Citation Tang, Qi, "CHEMICAL SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF METHYLATION AND GLYCATION DNA ADDUCTS" (2019). Open Access Dissertations. Paper 844. https://digitalcommons.uri.edu/oa_diss/844 This Dissertation is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Dissertations by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. CHEMICAL SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF METHYLATION AND GLYCATION DNA ADDUCTS BY QI TANG A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN PHARMACEUTICAL SCIENCES UNIVERSITY OF RHODE ISLAND 2019 DOCTOR OF PHILOSOPHY DISSERTATION OF QI TANG APPROVED: Dissertation Committee: Major Professor Deyu Li Bongsup Cho Gongqin Sun Nasser H. Zawia DEAN OF THE GRADUATE SCHOOL UNIVERSITY OF RHODE ISLAND 2019 ABSTRACT The integrity of genomic DNA is constantly challenged by endogenous and environmental agents with the formation of DNA adducts. Some of these adducts are toxic and mutagenic to replication, thus potentially leading to cancer and other genetic diseases. To counteract the undesired DNA modifications from damaging agents, cells have evolved a number of repair pathways, such as base-excision repair, nucleotide-excision repair, mismatch repair, and direct reversal repair, to restore the intact DNA. However, DNA repair is not always efficient, there are many interfering factors, such as inherited deficiency in DNA repair pathways, or the abnormal uptake of substance with inhibitory effects to DNA repair enzymes that may result in the accumulation of DNA adducts.
    [Show full text]
  • Chapter 1 Introduction
    The Cytotoxic Effects of Malondialdehyde on Human Lung Fibroblast Cells Sally Ann Yates A thesis submitted in partial fulfilment of the requirements of Liverpool John Moores University for the degree of Doctor of Philosophy March 2015 Abstract ABSTRACT Malondialdehyde (MDA) is a mutagenic and carcinogenic product of lipid peroxidation which has also been found at elevated levels in smokers. MDA reacts with nucleic acid bases to form pyrimidopurinone DNA adducts, of which 3-(2-deoxy-β-D-erythro- pentofuranosyl)pyrimidol[1,2-α]purin-10(3H)-one (M1dG) is the most abundant and has been linked to smoking. Mutations in the TP53 tumour suppressor gene are associated with half of all cancers. This research applied a multidisciplinary approach to investigate the toxic effects of MDA on the human lung fibroblasts MRC5, which have an intact p53 response, and their SV40 transformed counterpart, MRC5 SV2, which have a sequestered p53 response. Both cell lines were treated with MDA (0-1000 µM) for 24 and 48 h and subjected to a variety of analyses to examine cell proliferation, cell viability, cellular and nuclear morphology, apoptosis, p53 protein expression, DNA topography and M1dG adduct detection. For the first time, mutation sequencing of the 5’ untranslated region (UTR) of the TP53 gene in response to MDA treatment was carried out. The main findings were that both cell lines showed reduced proliferation and viability with increasing concentrations of MDA, the cell surface and nuclear morphology were altered, and levels of apoptosis and p53 protein expression appeared to increase. A LC-MS-MS method for detection of M1dG adducts was developed and adducts were detected in CT-DNA treated with MDA in a dose-dependent manner.
    [Show full text]
  • Copper Toxicity and Disease States: Wilson's Disease
    Copper Toxicity and Disease States: Wilson’s Disease Alexis Harris, Lilia Koelemay, Emily Howard Printing: This poster is 48” wide by 36” high. It’s designed to be printed on a ABSTRACT EFFECTS OF WILSON’S DISEASE COPPER TOXICITY AND WILSON’S large Though copper plays a vital role in the human body, an excess of inorganic copper Copper is oxidized by molecular Kayser-Fleischer rings are one of the most visible symptoms may be fatal. Patients with the genetic recessive Wilson’s Disease have an excess of oxygen to form free radicals that can of Wilson’s Disease.10 copper that provides reducing effects that form free radials and peroxides that may change the structure of hepatocyte cause damage to liver cells and the overall health of the body. organellar lipids and thiol-containing proteins, causing the liver damage seen in Wilson’s Disease.3 The Customizing the Content: superoxide produced or a thiol present in the cell can oxidize copper further to product hydrogen peroxide, The placeholders in this which can form oxidants that can • Chronic copper toxicity primarily affects the liver because it is the first place cleave DNA.4 copper is deposited after it enters the blood. ¹¹ • Manifested by Liver Cirrhosis (liver scar tissue) formatted for you. INTRODUCTION • Also causes the rupture of red blood cells (hemolysis) • Estimated lethal dose in adult human is 10-20 g¹¹ placeholders to add text, or click • Cupric and cuprous copper ions can both be reduced; and cuprous is capable of By definition, Wilson’s disease is a recessive genetic disorder that causes the body to Copper II normally reacting with hydrogen peroxide and forming the hydroxyl radical (strongest an icon to add a table, chart, remove copper inadequately.
    [Show full text]
  • Targeting Lipid Peroxidation for Cancer Treatment
    molecules Review Targeting Lipid Peroxidation for Cancer Treatment Sofia M. Clemente 1, Oscar H. Martínez-Costa 2,3 , Maria Monsalve 3 and Alejandro K. Samhan-Arias 2,3,* 1 Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; [email protected] 2 Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid (UAM), c/Arturo Duperier 4, 28029 Madrid, Spain; [email protected] 3 Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), c/Arturo Duperier 4, 28029 Madrid, Spain; [email protected] * Correspondence: [email protected] Academic Editor: Mauro Maccarrone Received: 29 September 2020; Accepted: 3 November 2020; Published: 5 November 2020 Abstract: Cancer is one of the highest prevalent diseases in humans. The chances of surviving cancer and its prognosis are very dependent on the affected tissue, body location, and stage at which the disease is diagnosed. Researchers and pharmaceutical companies worldwide are pursuing many attempts to look for compounds to treat this malignancy. Most of the current strategies to fight cancer implicate the use of compounds acting on DNA damage checkpoints, non-receptor tyrosine kinases activities, regulators of the hedgehog signaling pathways, and metabolic adaptations placed in cancer. In the last decade, the finding of a lipid peroxidation increase linked to 15-lipoxygenases isoform 1 (15-LOX-1) activity stimulation has been found in specific successful treatments against cancer. This discovery contrasts with the production of other lipid oxidation signatures generated by stimulation of other lipoxygenases such as 5-LOX and 12-LOX, and cyclooxygenase (COX-2) activities, which have been suggested as cancer biomarkers and which inhibitors present anti-tumoral and antiproliferative activities.
    [Show full text]
  • Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders
    Review Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders Giuseppina Barrera 1,*, Stefania Pizzimenti 1, Martina Daga 1, Chiara Dianzani 2, Alessia Arcaro 3, Giovanni Paolo Cetrangolo 3, Giulio Giordano 4, Marie Angele Cucci 1, Maria Graf 4 and Fabrizio Gentile 3 1 Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, 10124 Turin, Italy; [email protected] (S.P.); [email protected] (M.D.); [email protected] (M.A.C.) 2 Dipartimento di Scienze e Tecnologia del Farmaco, Università di Torino, 10124 Turin, Italy; [email protected] 3 Dipartimento di Medicina e Scienze della Salute “V. Tiberio”, Università del Molise, 86100 Campobasso, Italy; [email protected] (A.A.); [email protected] (G.P.C.); [email protected] (F.G.) 4 Presidio Ospedaliero “A. Cardarelli”, Azienda Sanitaria Regione Molise, 86100 Campobasso, Italy; [email protected] (G.G.); [email protected] (M.G.) * Correspondence: [email protected] Received: 29 June 2018; Accepted: 27 July 2018; Published: 30 July 2018 Abstract: Among the various mechanisms involved in aging, it was proposed long ago that a prominent role is played by oxidative stress. A major way by which the latter can provoke structural damage to biological macromolecules, such as DNA, lipids, and proteins, is by fueling the peroxidation of membrane lipids, leading to the production of several reactive aldehydes. Lipid peroxidation-derived aldehydes can not only modify biological macromolecules, by forming covalent electrophilic addition products with them, but also act as second messengers of oxidative stress, having relatively extended lifespans. Their effects might be further enhanced with aging, as their concentrations in cells and biological fluids increase with age.
    [Show full text]
  • Antioxidant Defenses and Lipid Peroxidation in Human Blood Plasma
    Proc. Natl. Acad. Sci. USA Vol. 85, pp. 9748-9752, December 1988 Medical Sciences Antioxidant defenses and lipid peroxidation in human blood plasma (oxidants/polymorphonuclear leukocytes/ascorbate/plasma peroxidase) BALZ FREI, ROLAND STOCKER*, AND BRUCE N. AMESt Department of Biochemistry, University of California, Berkeley, CA 94720 Contributed by Bruce N. Ames, August 12, 1988 ABSTRACT The temporal disappearance in human blood preventive treatment of atherosclerosis. Also, eliminating plasma of endogenous antioxidants in relation to the appear- lipid hydroperoxides in plasma before they are taken up into ance of various classes of lipid hydroperoxides measured by peripheral tissues might have a great impact on the various HPLC postcolumn chemiluminescence detection has been in- other diseases associated with oxidative stress. vestigated under two types ofoxidizing conditions. Exposure of Human plasma is endowed with an array of antioxidant plasma to aqueous peroxyl radicals generated at a constant rate defense mechanisms. Important plasma antioxidants appear leads immediately to oxidation of endogenous ascorbate and to be ascorbate (7), urate (8), a-tocopherol (9), albumin- sulfhydryl groups, followed by sequential depletion of biliru- bound bilirubin (10), and albumin itself (11). Protein sulfhy- bin, urate, and o!-tocopherol. Stimulating polymorphonuclear dryl groups have also been suggested to contribute signifi- leukocytes in plasma initiates very rapid oxidation ofascorbate, cantly to the antioxidant capacity of plasma (12), although
    [Show full text]
  • Relation of Antioxidants and Level of Dietary Lipid to Epidermal Lipid Peroxidation and Ultraviolet Carcinogenesis1
    [CANCER RESEARCH 45, 6254-6259, December 1985] Relation of Antioxidants and Level of Dietary Lipid to Epidermal Lipid Peroxidation and Ultraviolet Carcinogenesis1 Homer S. Black,2 Wanda A. Lenger, Janette Gerguis, and John I. Thornby Photobiology Laboratory [H. S. B., W. A. L, J. G.] and Biostatistics Section [J. I. T.], Veterans Administration Medical Center, and Department of Dermatology [H. S. B.¡, Baylor College of Medicine, Houston, Texas 77211 ABSTRACT that dietary fat enhanced the incidence of coal tar-induced skin tumors. This effect of dietary lipid upon chemical carcinogenesis It has become increasingly evident that both quantity and was soon substantiated and numerous studies have since been quality of dietary lipid can influence the developmental course of conducted on the quantitative and qualitative composition of several major forms of cancer in experimental animals. Using the dietary lipids and their relationship to tumor enhancement (4-9). hairless mouse-ultraviolet (UV) model, we had previously dem Generally, these studies have shown that animals fed high-fat onstrated that unsaturated lipid compared to equivalent levels of diets develop tumors more readily than cohorts fed low-fat diets. hydrogenated lipid enhanced photocarcinogenesis with respect Tumors of which this effect has been most often observed are to both tumor latency and multiplicity. In the present study using those of the skin, mammae, and intestine. High levels of fat the same model, we have examined the effect of unsaturated appear to exert maximum influence upon the promotional stages lipid level and antioxidants upon epidermal lipid peroxidation and of carcinogenesis (10). UV carcinogenesis. Sixteen groups of 45 animals each were With regard to quality of fat, it is polyunsaturated lipids which used in the study, representing all combinations of three design generally enhance tumorigenesis.
    [Show full text]
  • Vitamin E Attenuates Oxidative Stress Induced by Intravenous Iron in Patients on Hemodialysis
    J Am Soc Nephrol 11: 539–549, 2000 Vitamin E Attenuates Oxidative Stress Induced by Intravenous Iron in Patients on Hemodialysis JOHANNES M. ROOB,* GHOLAMALI KHOSCHSORUR,† ANDREAS TIRAN,‡ JORG¨ H. HORINA,* HERWIG HOLZER,* and BRIGITTE M. WINKLHOFER-ROOB§ *Division of Clinical Nephrology and Hemodialysis, Department of Internal Medicine, †Department of Laboratory Medicine I, ‡Department of Laboratory Medicine II, and §Institute of Biochemistry, Karl-Franzens University of Graz, Austria. Abstract. Intravenous iron application to anemic patients on cholesterol (5.88 Ϯ 1.09 mmol/mol) were normal, plasma hemodialysis leads to an “oversaturation” of transferrin. As a MDA concentrations were above normal (1.20 Ϯ 0.28 ␮mol/ result, non-transferrin-bound, redox-active iron might induce L), and bleomycin-detectable iron (BDI), indicating the pres- lipid peroxidation. To test the hypothesis that vitamin E atten- ence of redox-active iron, was not detectable. Upon iron infu- uates lipid peroxidation in patients receiving 100 mg of iro- sion, BDI and MDA concentrations increased significantly n(III) hydroxide sucrose complex intravenously during a he- (P Ͻ 0.001). BDI concentrations explained the increase over modialysis session, 22 patients were investigated in a baseline in MDA concentrations (MDA ϭ 1.29 ϩ 0.075 ϫ randomized cross-over design, either with or without a single BDI). Vitamin E supplementation, leading to a 68% increase in oral dose of 1200 IU of all-rac-␣-tocopheryl acetate taken 6 h plasma ␣-tocopherol concentrations, significantly reduced the ϭ before the hemodialysis session. Blood was drawn before and AUC0–180 min of MDA to cholesterol (P 0.004) and perox- 30, 60, 90, 135, and 180 min after the start of the iron infusion, ides to cholesterol (P ϭ 0.002).
    [Show full text]
  • Studies of Lipid Peroxidation, Its Link to Human Pathologies, and Isotopic Reinforcement of Polyunsaturated Fatty Acids As a Strategy to Reduce Oxidative Damage
    Studies of Lipid Peroxidation, its Link to Human Pathologies, and Isotopic Reinforcement of Polyunsaturated Fatty Acids as a Strategy to Reduce Oxidative Damage By Connor Reid Lamberson Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Chemistry May 31, 2017 Nashville, Tennessee Approved: Ned A. Porter, Ph.D. Lawrence J. Marnett, Ph.D. John A. McLean, Ph.D. Brian O. Bachmann, Ph.D. For Grandpa. Thank you for the memories and wisdom you imparted on me. ii ACKNOWLEDGEMENTS This work was made possible by generous support from the National Science Foundation grant, the National Institute of Health grant, funding from Retrotope, Inc., the Vanderbilt Institute for Chemical Biology and Vanderbilt University College of Arts and Science. First and foremost, I would like to extend my thanks and gratitude to my Ph.D. advisor, Professor Ned A. Porter. He provided the framework, support, and freedom for me to pursue my scientific interests over the past five years. He has been an excellent scientific mentor as well as a tremendous role model. His career exudes passion and drive, traits which have undoubtedly rubbed off on myself and countless other students over the years. I would also like to thank my dissertation committee members Dr. Lawrence J. Marnett, Dr. John A. McLean, and Dr. Brian O. Bachmann. They have all provided valuable suggestions and guidance through committee meetings as well as course work. All have at one time or another opened up their labs to me as well, allowing me to expand my scientific knowledge and skill all while broadening my horizons.
    [Show full text]
  • Measurement and Clinical Significance of Lipid Peroxidation
    antioxidants Review Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation Fumiaki Ito 1,*, Yoko Sono 2 and Tomoyuki Ito 3,4 1 The Institute of Prophylactic Pharmacology, Shinagawa, Tokyo 140-0001, Japan 2 R&D Department, Sunstar Inc., Takatsuki, Osaka 569-1195, Japan; [email protected] 3 Physical Medicine and Rehabilitation, Tanabe Memorial Hospital, Kyotanabe-City, Kyoto 610-0331, Japan; [email protected] 4 Department of Rehabilitation Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan * Correspondence: setsunanfi@zmail.plala.or.jp; Tel.: +81-743-79-3910 Received: 15 March 2019; Accepted: 20 March 2019; Published: 25 March 2019 Abstract: Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end products. Among these risk factors, oxidative stress is the largest contributor to the formation of atherosclerotic plaques. Measurement of reactive oxygen species (ROS) is still difficult, and assays for the measurement of ROS have failed to show a consistent correlation between pathological states and oxidative stress. To solve this problem, this review summarizes the current knowledge on biomarkers of oxidative stress, especially lipid peroxidation, and discusses the roles of oxidative stress, as measured by indices of lipid peroxidation, in diabetes mellitus, atherosclerosis, and chronic inflammation. Keywords: oxidative stress; oxidative stress biomarkers; lipid peroxidation; 8-isoprostaglandin F2α; malondialdehyde; Fe-ROMs test; diabetes mellitus; endothelial dysfunction; atherosclerosis; cardiovascular disease; chronic inflammation; oxidized high-density lipoprotein 1.
    [Show full text]